Texas Children’s Hospital

5th Annual
Advanced Practice Provider Conference

Anemia
UTD

Trinh Nguyen, DO
Assistant Professor Pediatrics
Hematology/Oncology
4-6-2018
Hemoglobin

Quinn, ASPHO 2013 lecture

Hemoglobin

Quinn, ASPHO 2013 lecture

Factors determining hemoglobin
values in normal children

• Age
• Gender
• Race
• Degree of sexual maturation
• Altitude
• Hereditary

Buchanan ASPHO 2013

Classification of Anemia

• Pathophysiologic mechanism
• Decreased production
• Increased destruction (Hemolysis)
• Sequestration
• Acute blood loss

• RBC size
• Microcytic
• Normocytic
• Macrocytic
Buchanan ASPHO 2013
Buchanan’s Rules of:

• Anemia
• 11 + [0.1 x (age in years)] = lower limit of normal for hgb

• MCV (Microcytosis)
• 70 + [1 x (age in years)] = lower limit of normal for MCV

• Example:
• 15 m/o hgb 11.2 gm/dL & MCV 74 = NORMAL
• 9 y/o hgb 10.9 gm/dL & MCV 71 = abNORMAL

Buchanan ASPHO 2013

 Definitions

• RBC# - number of RBCs in volume of

• WBC (5.0 - 14.5 10^3/UL) 12.60
blood
• RBC (3.9 - 5.3 10^6/UL) 3.37 (L) • Hct - ratio of RBCs to volume of whole
• Hgb (11.5 - 14.5 g/dL) 6.5 (L) blood
• HCT (34.0 - 40.0 %) 21.6 (L)
• MCV - average volume of red blood
• MCV (76.0 - 90.0 FL) 64.1 (L)
cells
• MCH (25.0 - 30.0 PG) 19.3 (L)
• MCHC (32.0 - 36.0 g/dL) 30.1 (L) • MCH - average amt of hemoglobin in
• RDW (11.5 - 15.0 %) 18.6 (H) the average rbc
• Platelet (150 - 450 10^3/UL) 263 • MCHC - average concentration of hgb
in a volume of blood
• RDW - variability of RBC size
 S/S/PE
• Pallor Fair-skinned • Hemolysis:
• • Icterus
https://www.google.com/search?biw=1920&bih=951&tbm=isch&sa=1&ei=NoCqWprVH https://www.google.com/search?biw=1920&bih=951&tbm=isch&sa=1&ei

Fatigue JLAtQXx6YDoDA&q=pale+tongue&oq=pale+tongue&gs_l=psy-
ab.3..0l10.1558.3615.0.3819.11.8.1.2.2.0.134.535.7j1.8.0....0...1c.1.64.psy-
ab..0.11.600...0i67k1.0 .bl8Is5mYgSc#imgrc=h83i1mnbuam0aM:
=NoCqWprVHJLAtQXx6YDoDA&q=pale+tongue&oq=pale+tongue&gs_
l=psy-ab.3..0l10.1558.3615.0.3819.11.8.1.2.2.0.134.53
5.7j1.8.0....0...1c.1.64.psy-

• Jaundice
ab..0.11.600...0i67k1.0.bl8Is5mYgSc#imgrc=DUPOwJ17r2HwmM:

• Feeding intolerance
• Darker urine (cola/tea)
• Activity intolerance
https://www.google.com/search?q=pale+conjunctiva
&tbm=isch&source=iu&ictx=1&fir=2IbSK-

• Gallstones early age

NXCn3ihM%253A%252CzFKH2-
giAfOjWM%252C
_&usg=__YxQUs2uUgoc2Blowo1LkQsBtJjQ%3D&

• Increased sleepiness
sa=X&ved=0ahUKEwj22qvhwe7ZAhUGR6wKHSm

• Splenomegaly
-AjYQ9QEIbDAM#imgrc=2IbSK-NXCn3ihM:

• Increased fussiness • Bleeding

• Lethargy • Pica
https://www.google.com/search?biw=1920&bih=951&tbm=isch&sa=1&ei=8YCq
WsiEJIa8sAWaj7y4Dw&q=iron+deficiency+anem
https://www.google.com/search?biw=1920&bih=951&tbm=isch&sa=1&ei=8YCq
WsiEJIa8sAWaj7y4Dw&q=iron+deficiency+anemia+nailbed&oq=iron+deficiency
ia+nailbed&oq=iron+deficiency+anemia+nailbed&gs_l=psy- +anemia+nailbed&gs_l=psy-ab.3..0i13k1.1759.921

• Tachycardia ab.3..0i13k1.1759.9218.0.9417.48.27.4.12.13.0.136.1508.24j1.25.0....0...1c.1.64.psy- 8.0.9417.48.27.4.12.13.0.136.1508.24j1.25.0....0...1c.1.64.psy-

• Musculoskeletal abnormalities
ab..10.37.1422...0j0i30k1j0i8i30k1j0i24k1j0i67k1j0i8i13i30k1.0.vFbpctJmc9Q#im ab..10.37.1422...0j0i30k1j0i8i30k1j0i24k1j0i67k1j0i8i13i30k1.0.vFbpctJmc9Q#img
grc=_TCvqP-otQYZNM: rc=2zXVHFMRZY05tM:

• Flow murmur
Evaluation

• CBC with d/p

• Reticulocyte Unstable  ER
• PBS

• Hemoglobin electrophoresis

• Total/Direct/Indirect Bili
• LDH
Others???
• Haptoglobin
• UA
https://samantha-brown.com/tips/6-things-to-consider-when-buying-luggage/
 Case 1

• 10 week old former term baby seen for well child

• ROS: Rhinorrhea, congestion, otherwise well,
active, afebrile
• Diet: Exclusively BF
• PMH: Negative
• Meds: None
• FH: Negative
• PE: Same as ROS
• Labs: CBC with d/p
Case 1

10
7.5 >------------------------------< 425
32

MCV = 92 MCH = 18
RDW = 14 RBC = 3.9
Diff = Normal
Case 1

• Transfuse?
• Next step?
 Case 1

• Physiologic Anemia of Early Infancy

Hgb <13.5 g/dL
• Hgb at birth 15-20 g/dL within first month
• Decrease during first 2-3 month of life
• Nadir
• Term: 10-12 weeks Hgb <9 g/dL

• Preemie: 6-8 weeks Hgb <7 g/dL *

Next step?
 Case 2

• 15 m/o HF  WCC (last seen 9 m/o)

• ROS: Doing well, no recent illnesses, very active,
walking, no concerns
• Diet: Exclusively BF till 12m/o, now whole milk, 40
ounces/day
• PMH: Negative
• Meds: None
• FH: Negative
• PE: Looked pale but active and otherwise benign
• Labs: CBC with d/p
Case 2

6.3
5.5 >------------------------------< 450
18.3

MCV = 55 MCH = 17
RDW = 18 RBC = 3.1
Diff = Normal
Case 2

• Transfuse?
• Next step?
Treatment

• Identify and treat cause of iron deficiency

• Oral iron therapy:

• 3 mg/kg/d elemental iron in a single daily dose for
mild iron deficiency
• 5-6 mg/kg/d elemental iron in 2 divided doses for
severe

• PRBC: severe cases (Hb < 4 g/dL)

Iron supplementation if exclusively breastfed past 6 m/o

Iron Rich Foods

TX

American Red Cross

PBS

Schrier, S. ASH Image Bank 2002;2002:100325

Copyright ©2002 American Society of Hematology. Copyright restrictions may apply.

Case 3

• 22 m/o AAF  WCC

• ROS: URI 5 weeks ago; now well, active, no
concerns
• Diet: Regular, loves meat, milk with cereal only
• PMH: Negative
• Meds: None
• FH: Negative
• PE: Looked pale
• Labs: CBC with d/p
Case 3

6.2
5.8 >--------------------------------< 412
18.5

MCV = 81 MCH = 27
RDW = 13 RBC = 2.43
Diff = Normal

12 m/o CBC normal

Case 3

• Transfuse?
• Next step?
Transient Erythroblastopenia of
Childhood (TEC)

• A form of Pure Red Cell Aplasia (PRCA)

• The most common form of PRCA
H&P
CBC
• Temporary
Retic
• Self limiting PBS
• Healthy child
• Normocytic anemia, reticulocytopenia, normal
PBS
• ~50% preceding viral illness
Bone Marrow
 Case 4

• 27 m/o Italian-American M  1st clinic visit

• ROS: Doing well, no recent illnesses, very active and
social
• Diet: Regular, loves meat, 6 oz/day milk
• PMH: Anemic at 12 m/o visit, tried iron x 6 months  no
improvement
• Meds: None
• FH: Several relatives anemic, on iron; no transfusions
• PE: Unremarkable
• Labs: CBC with d/p, retic, PBS
Case 4

10.8
6.5 >------------------------------< 496
32.7

MCV = 68 MCH = 27
RDW = 13 RBC = 5.9
Diff = Normal Retic 1.2
PBS

Microcytic

Target

UTD
Case 4

• Transfuse?
• Next step?
Case 4

10.8
6.5 >------------------------------< 496
32.7

MCV = 68 MCH = 27
RDW = 13 RBC = 5.9
Diff = Normal Retic 1.2

Mentzer index (MCV/RBC) = 11.5 < 13

Hemoglobin

Quinn, ASPHO 2013 lecture

 Hgb A = α2β2
Case 4: Thalassemias
Decreased production of α or β globins

Imbalance between α or β globins

Globins in excess precipitate and damage RBC membrane

Ineffective erythropoiesis

Anemia BM Extramedullary Intestinal

expansion hematopoiesis iron absorption
Quinn, ASPHO 2009 lecture
Thalassemias

• α thalassemia = defect in α globin gene

• β thalassemia = defect in β globin gene

• Severity
• Thalassemia minor – mild anemia, asymptomatic carrier (trait)
• Thalassemia intermedia – moderate anemia, prn prbcs
• Thalassemia major – severe anemia, prbc dependent

http://www.primehealthchannel.com/wp-content/uploads/2013/05/Thalassemia-Image.jpg
Quinn, ASPHO 2013 lecture
 Hgb A = α2β2
Case 5

• 4 week old  PCP office

• State screen results:
• Hgb F

Normal = F, A
Case 5

• Beta-Thalassemia
• aka Cooley’s Anemia

Hematology
 State Screen Results

Hgb A = α2β2 http://www.thalassemia.org/

Diagnosis

F,A Normal
F,A,V Heterozygous Variant
F Beta Thalassemia Major
F,S Sickle cell disease
SS or S-Beta null
F,S,C Sickle cell SC disease
F,S,A Sickle cell S-Beta disease
A,F ??????????????????
State Screen
State Screen

What does state screen NOT tell you?

Beta thalassemia trait

Case 6

• Pathology rotation — 4 y/o AAM admitted for fever

6.3
23.5 >------------------------------< 550
19.1
Retic 15%

MCV = 81 MCH = 30
RDW = 18 RBC = 3.9
Diff = 5B/50N/35L/9M
PBS
Sickle Cell Disease

• HbSS
• HbSβ0 thalassemia
• HbSβ+ thalassemia
• HbSC

• HbSα thalassemia
• HbSE………
https://coursewareobjects.elsevier.com/objects/elr/Lewis/medsurg8e/IC/jpg/Chapter31/031004.jpg
 Sickle Cell Disease

• PCN prophylaxis • Avoid infections,

• Vaccinations dehydration,
extremes of temperature
• MCV4
• MCV B serotype • Abx
• PCV13 • Hydrate
• PPSV23 • Pain control
• Transcranial doppler
• ECHO • Hydroxyurea
• Ophthalmology • Chronic prbcs
• Stem Cell Transplant
 Case 7

• 13 y/o AAF presents with fatigue, pallor

• ROS: UTI 13 days ago, currently afebrile, no UTI complaints
• PMH: Jaundiced at 18 HOL @ birth, no phototherapy
• UTI 2 weeks ago
• Meds: Bactrim x 10 days for UTI; none
• FH: GF with anemia  ?etiology
• PE: Slight icterus, pale mucous
membranes/nailbeds/palms/soles, tachycardic, II/VI SEM,
tired but answers questions appropriately
• Labs: CBC with d/p, retic, PBS
Case 7

7.8
7.3 >------------------------------< 355 Total bili 3.4
31.4 Direct bili 0.4
Indirect bili 2.9
LDH 784
MCV = 87 MCH = 29 Haptoglobin 20
RDW = 17 RBC = 4.5
Diff = 3B/ 45N/ 50L/ 2M
Retic 11.9
Case 7

UTD
Case 7

• Transfuse?
• Next step?

ER/Admit/Call Heme-Onc
Case 7

Hemolytic anemia

https://www.google.com/search?q=thinking+man&source=lnms&tbm=isch&sa=X&ved=0ahUKEwjQ06zM2O7ZAhUMQ6wKHZUID40Q_AUICigB&biw=1920&bih=951#imgrc=3EqzF8nC0xp0hM
:
Hemolytic Anemias

Intrinsic HA Extrinsic HA
• Hemoglobinopathy • Autoimmune
• RBC membrane hemolytic anemia
defect • Hypersplenism
• Enzyme deficiency • Systemic disease
• Drugs/toxins
• DIC/HUS/TTP
• Mechanical damage
Case 7

Only rbc source of NADPH  glutathione metabolism

S. Gomez-Manzo, et.al. Int J of Mol Sci 2016
G6PD
Females CAN have X-linked disorders

• Glucose 6 phosphate dehydrogenase deficiency

• X-linked recessive
• Most common enzymatic disorder of RBC
• New vs. old RBC
• Several variants
• Avoid: sulfas, dapsone, primaquine, methylene blue,
rasburicase, fava beans, naphthalene (mothballs), aniline
dye…

• http://www.g6pd.org/
G6PD

UTD
 Case 8

• 9 y/o CM with 4 day hx pallor, fatigue, icterus, jaundice, h/a

• ROS: URI last week, frequent RUQ abdominal pain x 6m, eyes
yellow when sick
• PMH: Neonatal hyperbilirubinemia HOL 16, s/p PRBCs;
Gallstones diagnosed 3 months ago
• Meds: MVI
• FH: Dad and MGM had splenectomy in teens and 20s,
respectively. Both had gallstones in their teens.
• PE: Pale, tired, sleepy, icteric, jaundice, tachycardic, II/VI SEM
• Labs: CBC with d/p, retic, PBS
Case 8

5.3
5.5 >---------------------------< 250 Retic 21
16
Total bili 9
MCV = 84 MCH = 33 Direct bili 0.8
MCHC = 37 Indirect bili 8.2
RDW = 17 RBC = 2.5 LDH 1189
Diff = 0B/ 25N/ 73L/ 2M Haptoglobin <10
PBS
Hereditary Spherocytosis:

• Most common cause of non-immune hemolytic anemia

• Autosomal Dominant transmission ~2/3
• 25-30% sporadic mutations
• Autosomal Recessive  more severe
• Loss of membrane surface area relative to intracellular
volumespheres and decreased deformability
• Membrane insufficiently tacked to cytoskeleton
• Abnormalities of spectrin and/or ankyrin
• Less common Protein 4.2 or Band 3
I. Andolfo, et.al. Haematologica 2016

Neufeld, ASPHO 2009 lecture

Case 9

• 4 y/o CF temp 101-102 x 2 weeks

• Bilateral leg pain
• Not eating well, maybe lost 3 pounds
• GM thinks she looks pale
• + Easy bruising
• Rash on legs
• ROS: As above, o/w negative
• PMH: Negative
• FH: Negative
• Meds: Negative
 Case 9

• PE: Temp 100.8, VSS

• Alert
• + Pallor
• Bruise on inner right thigh and left arm (medial
surface), petechiae at site of BP cuff
• II/VI systolic murmur
• LCTAB
• + BS, soft, NTTP, (?) HSM
• Cervical LAD, ~2cm right chains; 1.5cm left chain;
• Right supraclavicular LAD
• Neuro intact
Labs: CBC with d/p, retic, PBS
Case 9

7.1
1.5 >-----------------------------------------< 43
14.9

MCV = 84 MCH = 31
RDW = 11 RBC = 2.3
Diff = 3B/ 17N/ 78L/ 2M

ANC = 300
Case 9

• Transfuse?
• Next step?

ER/Admit/Call Heme-Onc
What if...
ER/Admit/Call Heme-Onc

6.2
450 >-----------------------------------------< 35
19

MCV = 105 MCH = 31

RDW = 18 RBC = 2.9
Diff = PENDING

Does this change management?

Acute Leukemia

• Initial treatment
• Abx (functionally neutropenic)
• Hydration 1.5-2 x MIVF  NO K
• Pain control (no NSAIDs, no ASA)

• Prevent Tumor Lysis Syndrome (TLS)

• Hyperkalemia
• Hyperuricemia
• Hyperphosphatemia
• Hypocalcemia
Acute Leukemia

• Control hyperuricemia
• Allopurinol
• Rasburicase

• Avoid hyperphosphatemia
• Phosphate binders

• Avoid K

• Avoid Ca
https://s-media-cache-ak0.pinimg.com/236x/50/5a/d3/505ad3c84cc53ef72fe113191580a23c.jpg